U2: combined ultrasonic microscopy and ultrafast optics for molecular imaging and therapy

We have developed an approach to molecular detection in which a nanoscale object, such as important biological macromolecules, is transduced by a very short (femtosecond) laser pulse into a microscale object directly detectable with ultrasound. We use ultrafast optics to transduce a nanoparticle into a microbubble. Nonlinear absorption of a light pulse, with high peak intensity but negligible pulse energy, produces highly localized disruption via laser-induced optical breakdown (LIOB). This process induces a broadband shock wave and a microbubble within the disruption site. Dendrimers are highly branched molecules serving as nearly ideal templates to form dendrimer nanocomposites (DNC). By trapping metallic domains, the LIOB threshold of the organic host in water and tissue can be considerably decreased. Of particular interest are biologically targeted DNCs. A combination of geometric targeting, through precise optical focusing, and biochemical targeting, with these nanoagents, represents a potentially attractive approach for molecular imaging and therapy. We use ultrasonic microscopy to monitor LIOB. Our results suggest that targeted photodisruption can operate in two regimes: one near threshold in which LIOB can be controlled to produce detectable microbubbles with little cellular injury (i.e., minimally invasive); the second at a different set of parameters where LIOB is highly destructive, killing labeled cells for therapy. There are numerous potential medical applications, including the significant problem of squamous cell carcinoma.